tbuckley/cabot-search huggingface dataset:
Quantitative and functional characterisation of extracellular vesicles after passive loading with hydrophobic or cholesterol-tagged small molecules
Authors: Gwenola Tréton, Claudia Sayer, Melanie Schürz, Maria Jaritsch, Anna Müller, Cristian-Tudor Matea, Vesna Stanojlovic, Heloisa Melo-Benirschke, Celine Be, Caroline Krembel, Stephane Rodde, Matthias Haffke, Samuel Hintermann, Andreas Marzinzik, Sébastien Ripoche, Constantin Blöchl, Julia Hollerweger, Daniela Auer, Chiara Cabrele, Christian G. Huber, Martin Hintersteiner, Trixie Wagner, Andreas Lingel, Nicole Meisner-Kober
Journal: Journal of Controlled Release (2023)

Extracellular vesicles (EVs) are nanosized intercellular messengers that bear enormous application potential as biological drug delivery vehicles. Much progress has been made for loading or decorating EVs with proteins, peptides or RNAs using genetically engineered donor cells, but post-isolation loading with synthetic drugs and using EVs from natural sources remains challenging. In particular, quantitative and unambiguous data assessing whether and how small molecules associate with EVs versus other components in the samples are still lacking. Here we describe the systematic and quantitative characterisation of passive EV loading with small molecules based on hydrophobic interactions - either through direct adsorption of hydrophobic compounds, or by membrane anchoring of hydrophilic ligands via cholesterol tags. As revealed by single vesicle imaging, both ligand types bind to CD63 positive EVs (exosomes), however also non-specifically to other vesicles, particles, and serum proteins. The hydrophobic compounds Curcumin and Terbinafine aggregate on EVs with no apparent saturation up to 106-107 molecules per vesicle as quantified by liquid chromatography - high resolution mass spectrometry (LC-HRMS). For both compounds, high density EV loading resulted in the formation of a population of large, electron-dense vesicles as detected by quantitative cryo-transmission electron microscopy (TEM), a reduced EV cell uptake and a toxic gain of function for Curcumin-EVs. In contrast, cholesterol tagging of a hydrophilic mdm2-targeted cyclic peptide saturated at densities of ca 104-105 molecules per vesicle, with lipidomics showing addition to, rather than replacement of endogenous cholesterol. Cholesterol anchored ligands did not change the EVs' size or morphology, and such EVs retained their cell uptake activity without inducing cell toxicity. However, the cholesterol-anchored ligands were rapidly shed from the vesicles in presence of serum. Based on these data, we conclude that (1) both methods allow loading of EVs with small molecules but are prone to unspecific compound binding or redistribution to other components if present in the sample, (2) cholesterol anchoring needs substantial optimization of formulation stability for in vivo applications, whereas (3) careful titration of loading densities is warranted when relying on hydrophobic interactions of EVs with hydrophobic compounds to mitigate changes in physicochemical properties, loss of EV function and potential cell toxicity.
Antioxidant nanoemulsion loaded with latanoprost enables highly effective glaucoma treatment
Authors: Xuemeng Guo, Junlei Zhang, Xu Liu, Yichao Lu, Yingying Shi, Xiang Li, Sije Wang, Jiaxin Huang, Huihui Liu, Huanli Zhou, Qingpo Li, Lihua Luo, Jian You
Journal: Journal of Controlled Release (2023)
Epigenetic responses to rhinovirus exposure in airway epithelial cells are correlated with key transcriptional pathways in chronic rhinosinusitis
Authors: Marcus M. Soliai, Atsushi Kato, Katherine A. Naughton, James E. Norton, Aiko I. Klinger, Robert C. Kern, Bruce K. Tan, Dan L. Nicolae, Robert P. Schleimer, Carole Ober, Jayant M. Pinto
Journal: Allergy (2023)

Abstract Background Viruses may drive immune mechanisms responsible for chronic rhinosinusitis with nasal polyposis (CRSwNP), but little is known about the underlying molecular mechanisms. Objectives To identify epigenetic and transcriptional responses to a common upper respiratory pathogen, rhinovirus (RV), that are specific to patients with CRSwNP using a primary sinonasal epithelial cell culture model. Methods Airway epithelial cells were collected at surgery from patients with CRSwNP (cases) and from controls without sinus disease, cultured, and then exposed to RV or vehicle for 48 h. Differential gene expression and DNA methylation (DNAm) between cases and controls in response to RV were determined using linear mixed models. Weighted gene co‐expression analysis (WGCNA) was used to identify (a) co‐regulated gene expression and DNAm signatures, and (b) genes, pathways, and regulatory mechanisms specific to CRSwNP. Results We identified 5585 differential transcriptional and 261 DNAm responses (FDR &lt;0.10) to RV between CRSwNP cases and controls. These differential responses formed three co‐expression/co‐methylation modules that were related to CRSwNP and three that were related to RV (Bonferroni corrected p &lt; .01). Most (95%) of the differentially methylated CpGs (DMCs) were in modules related to CRSwNP, whereas the differentially expressed genes (DEGs) were more equally distributed between the CRSwNP‐ and RV‐related modules. Genes in the CRSwNP‐related modules were enriched in known CRS and/or viral response immune pathways. Conclusion RV activates specific epigenetic programs and correlated transcriptional networks in the sinonasal epithelium of individuals with CRSwNP. These novel observations suggest epigenetic signatures specific to patients with CRSwNP modulate response to viral pathogens at the mucosal environmental interface. Determining how viral response pathways are involved in epithelial inflammation in CRSwNP could lead to therapeutic targets for this burdensome airway disorder.
News from EULAR
Journal: Annals of the Rheumatic Diseases (2023)

EULAR—The European Alliance of Associations for Rheumatology—is pleased to announce a change in its presidency, as Professor Annamaria Iagnocco, Italy, has stepped down as President and handed over the role to Professor Daniel Aletaha, Austria. Professor Aletaha will lead EULAR in its mission to improve the lives of people with rheumatic and musculoskeletal diseases (RMDs), build on EULAR’s successes and drive EULAR forward. He is committed to continuing the work of his predecessor and taking the organisation to even greater heights. The full press release is available at EULAR press releases %7C EULAR For recommendations relevant to patient audiences, EULAR provides a lay summary version in English and calls on all interested organisations to disseminate them and encourage the translation into their own language:
Complexation‐Induced Resolution Enhancement Pleiotropic Small Diameter Vascular Constructs with Superior Antibacterial and Angiogenesis Properties
Authors: Huilun Xu, Zhengjiang Liu, Yan Wei, Yinchun Hu, Liqin Zhao, Longfei Wang, Ziwei Liang, Xiaojie Lian, Weiyi Chen, Jiucun Wang, Zhaoyan Yu, Xudong Ma, Di Huang
Journal: Advanced Healthcare Materials (2023)

Abstract 3D printing has been widely applied for preparing artificial blood vessels, which will bring innovation to cardiovascular disorder intervention. However, the printing resolution and anti‐infection properties of small‐diameter vessels (Φ &lt; 6 mm) have been challenging in 3D printing. The primary objective of this research is to design a novel coaxial 3D‐printing postprocessing method for preparing small‐size blood vessels with improved antibacterial and angiogenesis properties. The coaxial printing resolution can be more conveniently improved. Negatively charged polyvinyl alcohol (PVA) and alginate (Alg) interpenetrating networks artificial vessels are immersed in positively charged chitosan (CTS) solution. Rapid dimensional shrinkage takes place on its outer surface through electrostatic interactions. The maximum shrinkage size of wall thickness can reach 61.2%. The vessels demonstrate strong antibacterial properties against Escherichia coli (98.8 ± 0.5%) and Staphylococcus aureus (97.6 ± 1.4%). In rat dorsal skin grafting experiments, Cu 2+ can promote angiogenesis by regulating hypoxia‐inducible factor‐1 pathway. No artificial blood vessel blockage occurs after 5 days of blood circulation in vitro.
Acute Stress Disorder, Posttraumatic Stress Disorder, and Depression in Disaster or Rescue Workers
Authors: Carol S. Fullerton, Robert J. Ursano, Leming Wang
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The events of Sept. 11, 2001, highlighted the importance of understanding the effects of trauma on disaster workers. To better plan for the health care of disaster workers, this study examined acute stress disorder, posttraumatic stress disorder (PTSD), early dissociative symptoms, depression, and health care utilization in disaster workers. METHOD: Exposed disaster workers (N=207) and unexposed comparison subjects (N=421) were examined at 2, 7, and 13 months after an airplane crash. RESULTS: Exposed disaster workers had significantly higher rates of acute stress disorder, PTSD at 13 months, depression at 7 months, and depression at 13 months than comparison subjects. Those who were younger and single were more likely to develop acute stress disorder. Exposed disaster workers with acute stress disorder were 3.93 times more likely to be depressed at 7 months. Those with high exposure and previous disaster experience or who had acute stress disorder were more likely to develop PTSD. Similarly, those who were depressed at 7 months were 9.5 times more likely to have PTSD. Those who were depressed at 13 months were 7.96 times more likely to also meet PTSD criteria. More exposed disaster workers than comparison subjects obtained medical care for emotional problems at 2, 7, and 13 months. Overall, 40.5% of exposed disaster workers versus 20.4% of comparison subjects had acute stress disorder, depression at 13 months, or PTSD. CONCLUSIONS: Exposed disaster workers are at increased risk of acute stress disorder, depression, or PTSD and seek care for emotional problems at an increased rate.
Combined cytotoxic and immune-stimulatory gene therapy using Ad-TK and Ad-Flt3L: Translational developments from rodents to glioma patients
Authors: Syed M. Faisal, Maria G. Castro, Pedro R. Lowenstein
Journal: Molecular Therapy (2023)

Gliomas are the most prevalent and devastating primary malignant brain tumors in adults. Despite substantial advances in understanding glioma biology, there have been no regulatory drug approvals in the US since bevacizumab in 2009 and tumor treating fields in 2011. Recent phase III clinical trials have failed to meet their prespecified therapeutic primary endpoints, highlighting the need for novel therapies. The poor prognosis of glioma patients, resistance to chemo-radiotherapy, and the immunosuppressive tumor microenvironment underscore the need for the development of novel therapies. Gene therapy-based immunotherapeutic strategies that couple the ability of the host immune system to specifically kill glioma cells and develop immunological memory have shown remarkable progress. Two adenoviral vectors expressing Ad-HSV1-TK/GCV and Ad-Flt3L have shown promising preclinical data, leading to FDA approval of a non-randomized, phase I open-label, first in human trial to test safety, cytotoxicity, and immune-stimulatory efficiency in high-grade glioma patients (NCT01811992). This review provides a thorough overview of immune-stimulatory gene therapy highlighting recent advancements, potential drawbacks, future directions, and recommendations for future implementation of clinical trials. Gliomas are the most prevalent and devastating primary malignant brain tumors in adults. Despite substantial advances in understanding glioma biology, there have been no regulatory drug approvals in the US since bevacizumab in 2009 and tumor treating fields in 2011. Recent phase III clinical trials have failed to meet their prespecified therapeutic primary endpoints, highlighting the need for novel therapies. The poor prognosis of glioma patients, resistance to chemo-radiotherapy, and the immunosuppressive tumor microenvironment underscore the need for the development of novel therapies. Gene therapy-based immunotherapeutic strategies that couple the ability of the host immune system to specifically kill glioma cells and develop immunological memory have shown remarkable progress. Two adenoviral vectors expressing Ad-HSV1-TK/GCV and Ad-Flt3L have shown promising preclinical data, leading to FDA approval of a non-randomized, phase I open-label, first in human trial to test safety, cytotoxicity, and immune-stimulatory efficiency in high-grade glioma patients (NCT01811992). This review provides a thorough overview of immune-stimulatory gene therapy highlighting recent advancements, potential drawbacks, future directions, and recommendations for future implementation of clinical trials.
Assessing the validity and clinical meaningfulness of skin pain response (NRS30) assessed using numerical rating scale in hidradenitis suppurativa: Results from the SUNSHINE and SUNRISE trials
Authors: Xiaoling Wei, Anna Passera, Elisa Muscianisi, Lorenz Uhlmann, Li Chen, Santiago G. Moreno, Ruvie Martin, Marc Vandemeulebroecke, Deborah Keefe, Shoba Ravichandran, Magdalena B. Wozniak
Journal: Journal of the American Academy of Dermatology (2023)
CD6-targeted antibody-drug conjugate as a new therapeutic agent for T cell lymphoma
Authors: Neetha Parameswaran, Liping Luo, Lingjun Zhang, Joel Chen, Frank P. DiFilippo, Charlie Androjna, David A. Fox, Sarah L. Ondrejka, Eric D. Hsi, Deepa Jagadeesh, Daniel J. Lindner, Feng Lin
Journal: Leukemia (2023)
Modeling human brain rhabdoid tumor by inactivating tumor suppressor genes in induced pluripotent stem cells
Authors: Timothy Hua, Yu Xue, Drishty B. Sarker, Sonia Kiran, Yan Li, Qing-Xiang Amy Sang
Journal: Bioactive Materials (2023)

Atypical teratoid/rhabdoid tumor (ATRT) is a rare childhood malignancy that originates in the central nervous system. Over ninety-five percent of ATRT patients have biallelic inactivation of the tumor suppressor gene SMARCB1. ATRT has no standard treatment, and a major limiting factor in therapeutic development is the lack of reliable ATRT models. We employed CRISPR/Cas9 gene-editing technology to knock out SMARCB1 and TP53 genes in human episomal induced pluripotent stem cells (Epi-iPSCs), followed by brief neural induction, to generate an ATRT-like model. The dual knockout Epi-iPSCs retained their stemness with the capacity to differentiate into three germ layers. High expression of OCT4 and NANOG in neurally induced knockout spheroids was comparable to that in two ATRT cell lines. Beta-catenin protein expression was higher in SMARCB1-deficient cells and spheroids than in normal Epi-iPSC-derived spheroids. Nucleophosmin, Osteopontin, and Ki-67 proteins were also expressed by the SMARCB1-deficient spheroids. In summary, the tumor model resembled embryonal features of ATRT and expressed ATRT biomarkers at mRNA and protein levels. Ribociclib, PTC-209, and the combination of clofilium tosylate and pazopanib decreased the viability of the ATRT-like cells. This disease modeling scheme may enable the establishment of individualized tumor models with patient-specific mutations and facilitate high-throughput drug testing.
STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway
Authors: Jan Pencik, Cecile Philippe, Michaela Schlederer, Emine Atas, Matteo Pecoraro, Sandra Grund-Gröschke, Wen Li, Amanda Tracz, Isabel Heidegger, Sabine Lagger, Karolína Trachtová, Monika Oberhuber, Ellen Heitzer, Osman Aksoy, Heidi A. Neubauer, Bettina Wingelhofer, Anna Orlova, Nadine Witzeneder, Thomas Dillinger, Elisa Redl, Georg Greiner, David D’Andrea, Johnny R. Östman, Simone Tangermann, Ivana Hermanova, Georg Schäfer, Felix Sternberg, Elena E. Pohl, Christina Sternberg, Adam Varady, Jaqueline Horvath, Dagmar Stoiber, Tim I. Malcolm, Suzanne D. Turner, Eileen E. Parkes, Brigitte Hantusch, Gerda Egger, Stefan Rose-John, Valeria Poli, Suneil Jain, Chris W. D. Armstrong, Gregor Hoermann, Vincent Goffin, Fritz Aberger, Richard Moriggl, Arkaitz Carracedo, Cathal McKinney, Richard D. Kennedy, Helmut Klocker, Michael R. Speicher, Dean G. Tang, Ali A. Moazzami, David M. Heery, Marcus Hacker, Lukas Kenner
Journal: Molecular Cancer (2023)

Abstract Prostate cancer (PCa) is a common and fatal type of cancer in men. Metastatic PCa (mPCa) is a major factor contributing to its lethality, although the mechanisms remain poorly understood. PTEN is one of the most frequently deleted genes in mPCa. Here we show a frequent genomic co-deletion of PTEN and STAT3 in liquid biopsies of patients with mPCa. Loss of Stat3 in a Pten -null mouse prostate model leads to a reduction of LKB1/pAMPK with simultaneous activation of mTOR/CREB, resulting in metastatic disease. However, constitutive activation of Stat3 led to high LKB1/pAMPK levels and suppressed mTORC1/CREB pathway, preventing mPCa development. Metformin, one of the most widely prescribed therapeutics against type 2 diabetes, inhibits mTORC1 in liver and requires LKB1 to mediate glucose homeostasis. We find that metformin treatment of STAT3/AR-expressing PCa xenografts resulted in significantly reduced tumor growth accompanied by diminished mTORC1/CREB, AR and PSA levels. PCa xenografts with deletion of STAT3/AR nearly completely abrogated mTORC1/CREB inhibition mediated by metformin. Moreover, metformin treatment of PCa patients with high Gleason grade and type 2 diabetes resulted in undetectable mTORC1 levels and upregulated STAT3 expression. Furthermore, PCa patients with high CREB expression have worse clinical outcomes and a significantly increased risk of PCa relapse and metastatic recurrence. In summary, we have shown that STAT3 controls mPCa via LKB1/pAMPK/mTORC1/CREB signaling, which we have identified as a promising novel downstream target for the treatment of lethal mPCa.
A Photo‐Activated Continuous Reactive Oxygen Species Nanoamplifier for Dual‐Dynamic Cascade Cancer Therapy
Authors: Xu Zhang, Xinlu Zhang, Haizhen Guo, Shitian Jia, Yong Li, Suixin Xing, Jin Chang, Sheng Wang
Journal: Advanced Healthcare Materials (2023)

The special redox homeostasis of tumor cells makes reactive oxygen species (ROS)-based approaches a promising cancer therapeutic strategy. Among these approaches, photodynamic therapy is the most widely studied ROS-based treatment due to its ability to achieve targeted therapy by local light irradiation. However, achieving efficient and continuous ROS generation without prolonged laser exposure is still challenging. In this work, a photo-activated continuous ROS nanoamplifier is proposed for photodynamic-chemodynamic cascade therapy. Upon local laser irradiation, the nanoamplifier can continuously amplify cellular oxidative stress through a positive feedback loop of "light-triggered ROS generation, ROS-responsive prodrug activation, and Fenton reaction-mediated ROS cyclic regenerative amplification", avoiding tissue damage caused by excessive laser exposure. This strategy provides a potential pathway to overcome the limitations of ROS-based therapeutic approaches.
Retraction Note: N6-methyladenosine induced mir-143-3p promotes the brain metastasis of lung cancer via regulation of VASH1
Authors: Hongsheng Wang, Qianqian Deng, Ziyan Lv, Yuyi Ling, Xue Hou, Zhuojia Chen, Xiaoxiao Dinglin, Shuxiang Ma, Delan Li, Yingmin Wu, Yanxi Peng, Hongbing Huang, Likun Chen
Journal: Molecular Cancer (2023)
A multicenter study on two-stage transfer learning model for duct-dependent CHDs screening in fetal echocardiography
Authors: Jiajie Tang, Yongen Liang, Yuxuan Jiang, Jinrong Liu, Rui Zhang, Danping Huang, Chengcheng Pang, Chen Huang, Dongni Luo, Xue Zhou, Ruizhuo Li, Kanghui Zhang, Bingbing Xie, Lianting Hu, Fanfan Zhu, Huimin Xia, Long Lu, Hongying Wang
Journal: npj Digital Medicine (2023)

Abstract Duct-dependent congenital heart diseases (CHDs) are a serious form of CHD with a low detection rate, especially in underdeveloped countries and areas. Although existing studies have developed models for fetal heart structure identification, there is a lack of comprehensive evaluation of the long axis of the aorta. In this study, a total of 6698 images and 48 videos are collected to develop and test a two-stage deep transfer learning model named DDCHD-DenseNet for screening critical duct-dependent CHDs. The model achieves a sensitivity of 0.973, 0.843, 0.769, and 0.759, and a specificity of 0.985, 0.967, 0.956, and 0.759, respectively, on the four multicenter test sets. It is expected to be employed as a potential automatic screening tool for hierarchical care and computer-aided diagnosis. Our two-stage strategy effectively improves the robustness of the model and can be extended to screen for other fetal heart development defects.
Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study
Authors: Emek Kocatürk, Pascale Salameh, Esra Sarac, Carolina E. Vera Ayala, Simon Francis Thomsen, Torsten Zuberbier, Luis Felipe Ensina, Todor A. Popov, Martijn B.A. van Doorn, Ana Maria Giménez-Arnau, Riccardo Asero, Paulo Ricardo Criado, Fernando M. Aarestrup, Zainab AbdulHameed Ansari, Salma Al Abri, Mona Al-Ahmad, Bushra Al Hinai, Anastasiia Allenova, Maryam Al-Nesf, Sabine Altrichter, Rand Arnaout, Joanna Bartosińska, Andrea Bauer, Jonathan A. Bernstein, Mojca Bizjak, Hanna Bonnekoh, Laurence Bouillet, Zenon Brzoza, Ana Caroline Calvalcanti Dela Bianca Melo, Fernanda L. Campinhos, Emily Carne, Saleema Cherichi Purayil, Ivan Cherrez-Ojeda, Herberto Jose Chong-Neto, George Christoff, Niall Conlon, Roberta Fachini Jardim Criado, Klara Cvenkel, Ebru Damadoglu, Inna Danilycheva, Cascia Day, Laurence de Montjoye, Semra Demir, Silvia Mariel Ferucci, Daria Fomina, Atsushi Fukunaga, Elizabeth Garcia, Asli Gelincik, Joe Hannah Göbel, Kiran Godse, Margarida Gonçalo, Maia Gotua, Clive Grattan, Agata Gugala, Carole Guillet, Ali Fuat Kalyoncu, Gul Karakaya, Alicja Kasperska-Zając, Constance H. Katelaris, Maryam Khoshkhui, Andreas Kleinheinz, Marta Kolacinska-Flont, Pavel Kolkhir, Mitja Košnik, Dorota Krasowska, Muthu Sendhil Kumaran, Izabela Kuprys-Lipinska, Marcin Kurowski, Elizaveta V. Kuznetsova, Désirée Larenas-Linnemann, Marina S. Lebedkina, Youngsoo Lee, Michael Makris, René Maximiliano Gómez, Iman Nasr, Sophia Neisinger, Yoshiko Oda, Rabia Öztaş Kara, Esther Bastos Palitot, Niki Papapostolou, Claudio Alberto Salvador Parisi, David Pesque, Jonathan Peter, Elena Petkova, Katie Ridge, Michael Rudenko, Krzysztof Rutkowski, Sarbjit S. Saini, Andac Salman, Jorge Sanchez, Bülent Şekerel, Sofia A. Serdotetskova, Faradiba S. Serpa, Bahar Sevimli Dikicier, Nikitas Sidiropoulos, Agnieszka Sikora, Jennifer Astrup Sørensen, Angele Soria, Ozlem Su Kucuk, Sherin Rahim Thalappil, Katarzyna Tomaszewska, Gulseren Tuncay, Derya Unal, Solange Valle, Esmee van Lindonk, Christian Vestergaard, Raisa Y. Meshkova, Aleksandr Vitchuk, Paraskevi Xepapadaki, Young-Min Ye, Anna Zalewska-Janowska, Mateusz Zamlynski, Marcus Maurer
Journal: Journal of Allergy and Clinical Immunology (2023)